Assisted Reproductive Technology (ART) has revolutionized treatment of human infertility in the past 30 years and has become standard practice in the U.S., where it accounts for over 1% of births. There are approximately 400 ART clinics in the U.S., which perform ˜150,000 cycles per year (˜900,000 cycles are performed worldwide per year), driving a multibillion dollar market. Despite wide spread use of ART, treatment is expensive and success rates are low: A cycle typically costs $10,000-$20,000 and only 10%-35% of cycles result in successful births. Patients are often tempted to have multiple embryos transferred in a single cycle to improve the odds of productive pregnancy, but this practice gives rise to high rates of multiple gestations. Multiple gestations greatly increase mortality rates and suffering for both infant and mothers, and produce substantial emotional and financial costs. Complications from multiple pregnancies from ART account for an estimated $1 billion of health care cost annually in the U.S. Therefore, there is a great need for technology which can increase the success rate and reduce the cost of ART.
In a typical ART treatment cycle, eggs are first retrieved from the patient and fertilized in vitro. One to three embryos are selected to transfer back to the patient, while the rest are frozen. If the patient becomes pregnant and gives birth to a healthy child, then the process is complete. If the pregnancy is unsuccessful, then the frozen embryos can be retrieved and transferred back to the patient, for another attempt at pregnancy.
One major reason for the low success rate of ART is the variable quality of eggs. Many factors contribute to egg quality in a manner that remains poorly understood, but it is known that only a subset of eggs collected from patients are at an appropriate stage of maturation. The fraction of immature eggs varies between patient populations and has not been well quantified, but values around 30% have been reported.
There has been substantial effort in both academia and industry to develop improved methods to measure egg and embryo quality, which would enable the healthiest embryos to be selected for implantation. The current method of predicting embryo quality is to examine embryo morphology prior to transfer using transmitted light microscopy systems, but that selection criterion is subjective and only produces the ˜10%-35% success rate quoted above. Other methods being developed to determine egg and embryo quality include genomic, transcriptomic or proteomic assays, which require a biopsy of the embryo, and are thus highly invasive and severely reduce embryo survival rates. An alternative approach is to assay the metabolic state of the embryo by doing experiments to measure changes in metabolites in the embryo culture media, but this is indirect and has proven challenging, and can adversely affect the embryo due to the need to change metabolite levels. So far, none of these alternative methods have been clinically proven to be more successful than the traditionally used approach of examining embryo morphology with transmitted light microscopy.